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Cannabinoid Receptor CB1 Is Involved in Nicotine-Induced Protection Against Aβ1–42 Neurotoxicity in HT22 Cells

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Abstract

Emerging evidences suggest that nicotine exerts a neuroprotective effect on Alzheimer’s disease (AD), yet the precise mechanism is not fully elucidated. Here, HT22 cells were exposed to amyloid beta protein fragment (Aβ)1–42 to mimic the pathological process of neuron in AD. We hypothesized that cannabinoid receptor CB1 is involved in the nicotine-induced neuroprotection against Aβ1–42 injury in HT22 cells. CB1 expression in HT22 cells was investigated by immunocytochemistry and Western blot. The injury of HT22 cells was evaluated by cellular morphology, cell viability, and lactate dehydrogenase (LDH) release. The apoptosis of HT22 cells was assessed by flow cytometry and expressions of Bcl-2 and Bax. The results demonstrated that nicotine markedly upregulated CB1 expression, increased cell viability, ameliorated cellular morphology, decreased LDH release, and reduced the apoptotic rate of HT22 cells exposed to Aβ1–42 for 24 h, while the blockade of CB1 or the inhibition of protein kinase C (PKC) partially reversed the neuroprotection. Furthermore, the blockade of CB1 reversed nicotine-induced PKC activation in HT22 cells exposed to Aβ1–42. These results suggest that CB1 is involved in the nicotine-induced neuroprotection against Aβ1–42 neurotoxicity, and the neuroprotection may be dependent on the activation of PKC.

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Abbreviations

Aβ:

Amyloid beta protein fragment

AD:

Alzheimer’s disease

ANOVA:

Analysis of variance

BSA:

Bovine serum albumin

CB1:

Cannabinoid receptor CB1

CB2:

Cannabinoid receptor CB2

DAPI:

4′,6-Diamidino-2-phenylindole

DMEM:

Dulbecco’s modified Eagle’s medium

DMSO:

Dimethyl sulfoxide

EA:

Electroacupuncture

LDH:

Lactate dehydrogenase

MTT:

3-(4,5-Dimethyl-2-thiazolyl)-2,5-diphenyl-2-tetrazolium bromide

PBS:

Phosphate-buffered saline

NMDA:

N-methyl-d-aspartate

PKC:

Protein kinase C

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Acknowledgments

This work was funded by the National Natural Science Foundation of China (Nos. 81072888 and 81171237).

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Authors and Affiliations

  1. Department of Anesthesiology, Xijing Hospital, The Fourth Military Medical University, Xi’an, 710032, China

    Mingchun Wu, Ji Jia, Chong Lei, Xiaodan Chen, Hanfei Sang & Lize Xiong

  2. Department of Anesthesiology, Tangdu Hospital, The Fourth Military Medical University, Xi’an, 710038, China

    Ling Ji

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  1. Mingchun Wu
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  2. Ji Jia
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  3. Chong Lei
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  4. Ling Ji
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  5. Xiaodan Chen
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  6. Hanfei Sang
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  7. Lize Xiong
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Corresponding authors

Correspondence to Hanfei Sang or Lize Xiong.

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Mingchun Wu Ji Jia and Chong Lei contributed equally to this work.

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Wu, M., Jia, J., Lei, C. et al. Cannabinoid Receptor CB1 Is Involved in Nicotine-Induced Protection Against Aβ1–42 Neurotoxicity in HT22 Cells. J Mol Neurosci 55, 778–787 (2015). https://doi.org/10.1007/s12031-014-0422-4

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  • DOI: https://doi.org/10.1007/s12031-014-0422-4

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